Ying Jie Zhu

Blood lymphocyte-to-monocyte ratio identifies high-risk patients in diffuse large B-cell lymphoma treated with R-CHOP

Background Recent research has shown a correlation between immune microenvironment and lymphoma biology. This study aims to investigate the prognostic significance of the immunologically relevant lymphocyte-to-monocyte ratio (LMR), in diffuse large B-cell lymphoma (DLBCL) in the rituximab era. Methodology/Principal Findings We analyzed retrospective data from 438 newly diagnosed DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. We randomly selected 200 patients (training set) to generate a cutoff value for LMR by receiver operating characteristic (ROC) curve analysis. LMR was then analyzed in a testing set (n = 238) and in all patients (n = 438) for validation. The LMR cutoff value for survival analysis determined by ROC curve in the training set was 2.6. Patients with low LMR tended to have more adverse clinical characteristics. Low LMR at diagnosis was associated with worse survival in DLBCL, and could also identify high-risk patients in the low-risk IPI category. Multivariate analysis identified LMR as an independent prognostic factor of survival in the testing set and in all patients. Conclusions/Significance Baseline LMR, a surrogate biomarker of the immune microenvironment, is an effective prognostic factor in DLBCL patients treated with R-CHOP therapy. Future prospective studies are required to confirm our findings.

Beclin 1 expression predicts favorable clinical outcome in patients with diffuse large B-cell lymphoma treated with R-CHOP

Beclin 1 plays a critical role not only in autophagy, but also in apoptosis and differentiation. The prognostic significance of beclin 1 in diffuse large B-cell lymphoma is largely unexplored. Immunohistochemical protein expression of beclin 1 in 118 tumor specimens from patients newly diagnosed with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone regimen from 2003 to 2007 was analyzed. Beclin 1 expression was observed in 101 (85.6%) patients. Low beclin 1 expression was related to B symptoms (P = .018), advanced Ann Arbor stage (P = .009), International Prognostic Index of 2 or higher (P = .049), elevated serum lactate dehydrogenase level (P = .037), and poor outcome using the revised International Prognostic Index model (P = .013). The complete remission rate after standard treatment was higher in patients with high beclin 1 expression than in those with low beclin 1 expression (77.5% versus 55.3%, P = .013). Beclin 1 expression was inversely associated with bcl-2 expression (P = .019) and positively associated with longer overall survival (P = .035) and progression-free survival (P = .013). In multivariate analysis, beclin 1 expression and the revised International Prognostic Index model independently predicted survival. The proposed clinicopathologic prognostic model including these 2 independent prognostic factors allowed classification of patients into 3 risk groups (P < .0001, respectively). Beclin 1 expression predicts superior clinical outcome in patients with diffuse large B-cell lymphoma treated with standard treatment. The novel prognostic model which divides patients with diffuse large B-cell lymphoma into different risk categories may help guide treatment planning.

Prognostic significance of peripheral monocyte count in patients with extranodal natural killer/T-cell lymphoma

BackgroundExtranodal natural killer/T-cell lymphoma (ENKL) has heterogeneous clinical manifestations and prognosis. This study aims to evaluate the prognostic impact of absolute monocyte count (AMC) in ENKL, and provide some immunologically relevant information for better risk stratification in patients with ENKL.MethodsRetrospective data from 163 patients newly diagnosed with ENKL were analyzed. The absolute monocyte count (AMC) at diagnosis was analyzed as continuous and dichotomized variables. Independent prognostic factors of survival were determined by Cox regression analysis.ResultsThe AMC at diagnosis were related to overall survival (OS) and progression-free survival (PFS) in patients with ENKL. Multivariate analysis identified AMC as independent prognostic factors of survival, independent of International Prognostic Index (IPI) and Korean prognostic index (KPI). The prognostic index incorporating AMC and absolute lymphocyte count (ALC), another surrogate factor of immune status, could be used to stratify all 163 patients with ENKL into different prognostic groups. For patients who received chemotherapy followed by radiotherapy (102 cases), the three AMC/ALC index categories identified patients with significantly different survivals. When superimposed on IPI or KPI categories, the AMC/ALC index was better able to identify high-risk patients in the low-risk IPI or KPI category.ConclusionThe baseline peripheral monocyte count is shown to be an effective prognostic indicator of survival in ENKL patients. The prognostic index related to tumor microenvironment might be helpful to identify high-risk patients with ENKL.

High Ki-67 expression in diffuse large B-cell lymphoma patients with non-germinal center subtype indicates limited survival benefit from R-CHOP therapy.

Objectives:  Rituximab has significantly improved the survival of patients with DLBCL, especially those with non‐germinal center B‐cell‐like (non‐GCB) subtype. The impact of Ki‐67 expression, an index of proliferation, on the clinical outcomes of patients with DLBCL has largely been unexplored. This study aimed to investigate whether Ki‐67 expression is an indicator of outcome in DLBCL patients (especially non‐GCB DLBCL patients) treated with standard chemotherapy combined with rituximab.

Primary mediastinal large B-cell lymphoma (PMLBCL) in Chinese patients: clinical characteristics and prognostic factors

Primary mediastinal large B-cell lymphoma (PMLBCL) is a unique clinico-pathological subtype, for which there is no optimal therapy yet. We evaluated clinical characteristics and prognostic factors in 39 consecutive, previously untreated Chinese patients with PMLBCL. The median age was 28 years (range 16–72 years). The majority of patients were stage I/II (23 cases, 59%). Bulky mediastinal mass was present in 18 cases (46%). The 3-year overall survival (OS) and progression-free survival (PFS) rates were 70 and 64%, respectively. Cox regression analysis showed that low serum albumin was an independent prognostic predictor of both OS (P = 0.002) and PFS (P = 0.001). Other prognostic factors for OS were extra-thoracic involvement (P = 0.016) and B symptoms (with borderline significance, P = 0.053). The addition of radiotherapy to chemotherapy seemed to have a favourable impact on OS (P = 0.034) and PFS (P = 0.039). The addition of rituximab to chemotherapy improved the survival trend, but added no significant benefit (OS: 57 vs. 84%, P = 0.287; PFS: 53 vs. 73%, P = 0.371). Our data additionally suggest that low serum albumin is a novel prognostic predictor for PMLBCL, and could be useful in determining treatment options in the clinic.

Clinical characteristics of the patients with Hodgkin＇s lymphoma involving extranodal sites

Differences between Hodgkins lymphoma (HL) patients in China and Western countries are known to exist, but data on Chinese patients with HL are limited. It is not clear whether there are clinical and histological differences in patients with HL involving different extranodal sites. This is the first study to analyze Chinese patients with HL involving different extranodal sites. We selected 22 HL patients with extranodal involvement from more than 250 previously untreated HL patients. Most patients were young males, and 20 of the 22 patients had stage IV disease. The major pathologic types were nodular sclerosis classical HL (NSCHL) and mixed cellularity classical HL (MCCHL). At diagnosis, the most commonly involved extranodal sites were the liver and lung, followed by the bones. There was no significant association between the international prognostic score (IPS) and survival in patients with different extranodal sites. Our data showed the overall survival (OS) and disease-free survival (DFS) rates of low-risk group (IPS = 0-2) were relatively higher than those of high-risk group (IPS ≥ 3), but the IPS did not show predictive power for survival. Although HL with extranodal involvement is rare, it should be considered as a unique form of HL.